title: Role of 6-gingerol in reduction of cholera toxin activity in vitro and in vivo.
abstract: Vibrio cholerae is one of the major bacterial pathogens responsible for the devastating diarrheal disease called cholera. Chemotherapy is often used against V. cholerae infections; however, the emergence of V. cholerae with multidrug resistance (MDR) toward the chemotherapeutic agents is a serious clinical problem. This scenario has provided us with the impetus to look into herbal remediation, especially toward blocking the action of cholera toxin (CT). Our studies were undertaken to determine the antidiarrheal potential of 6-gingerol (6G) on the basis of its effect on CT, the virulence factor secreted by V. cholerae. We report here that 6G binds to CT, hindering its interaction with the GM1 receptor present on the intestinal epithelial cells. The 50% inhibitory concentration (IC50) was determined to be 10 μg/ml. The detailed mechanistic study was conducted by enzyme-linked immunosorbent assay (ELISA), fluorescence spectroscopy, and isoelectric focusing. These results were validated with in vitro studies performed with the CHO, HeLa, and HT-29 cell lines, whereas a rabbit ileal loop assay was done to estimate the in vivo action, which confirms the efficacy of 6G in remediation of the choleragenic effects of CT. Thus, 6G can be an effective adjunctive therapy with oral rehydration solution for severe CT-mediated diarrhea.
authors.affiliation: Molecular and Human Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Pallashri
authors.initials: P
authors.lastname: Saha
authors.forename: Bornita
authors.initials: B
authors.lastname: Das
authors.forename: Keya
authors.initials: K
authors.lastname: Chaudhuri
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000930:Antidiarrheals / Q000302:isolation & purification / Q000494:pharmacology*; D016466:CHO Cells; D002396:Catechols / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002771:Cholera / Q000188:drug therapy / Q000382:microbiology; D002772:Cholera Toxin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D005233:Fatty Alcohols / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000382:microbiology; D020128:Inhibitory Concentration 50; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014734:Vibrio cholerae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000930:Antidiarrheals; D002396:Catechols; D005233:Fatty Alcohols; D011956:Receptors, Cell Surface; C034993:ganglioside receptor; D002772:Cholera Toxin; C007845:gingerol